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International Immunology Advance Access originally published online on January 13, 2006
International Immunology 2006 18(3):459-464; doi:10.1093/intimm/dxh386
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Pasteurella multocida toxin (PMT) activates RhoGTPases, induces actin polymerization and inhibits migration of human dendritic cells, but does not influence macropinocytosis

Dagmar Blöcker1,*, Luciana Berod2,*, Joachim W. Fluhr2, Joachim Orth1, Marco Idzko3, Klaus Aktories1 and Johannes Norgauer2

1 Department of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, D-79104 Freiburg, Germany
2 Department of Dermatology, Friedrich Schiller University, Erfurter Strasse 35, D-07740 Jena, Germany
3 Department of Pneumology, University of Freiburg, D-79104 Freiburg, Germany

Correspondence to: J. Norgauer; E-mail: johannes.norgauer{at}med.uni-jena.de

Dendritic cells (DCs) are considered as one of the principal initiators of immune responses. In their immature state, they migrate into peripheral tissue in order to uptake antigen and to patrol for danger signals. Upon maturation, they acquire the ability to migrate to the lymph nodes and present the captured antigens to T cells in order to direct the development of specific immune responses. There is evidence that microbial compounds interfere with proper functions of DCs in order to block innate and specific immunity. Here we characterized the influence of Pasteurella multocida toxin (PMT) on monocyte-derived DCs. Using pull-down assays with recombinant rhotekin or p21-activated kinase, we demonstrated the activation of RhoGTPases by PMT in DCs. Moreover, PMT induced changes in DC morphology and actin polymerization, impaired chemotaxin-induced actin re-organization and inhibited their migration response. However, macropinocytosis was not influenced by PMT. In summary, these data indicate that PMT inhibits proper function of the motility machinery in DCs, which might limit the development of adaptive immune surveillance during infection with Pasteurella multocida.

Keywords: actin, dendritic cells, migration, Pasteurella multocida toxin

* These authors contributed equally to this manuscript.

Transmitting editor: M. Reth


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